Azathioprine eases MG symptoms, but does not extend survival: Study
Long-term use linked to serious blood problems, cases of cancer
Azathioprine did not outperform standard treatment in helping adults with myasthenia gravis (MG) live longer, and while older age alone increased the risk of death, using azathioprine for many years was linked to serious blood problems and cases of cancer, a study has found.
However, “although the use of [azathioprine] had no influence on survival, it was of benefit for decreasing exacerbations and sparing corticosteroids,” wrote Pedro J. Modrego, MD, at Miguel Servet University Hospital in Spain, who conducted the study. He noted azathioprine “with the lowest dose of corticosteroids remains a first line treatment in many countries and guidelines.”
The study, “Long-Term Adverse Effects and Survival in Patients with Myasthenia Gravis Treated with Azathioprine: A Retrospective Cohort,” was published in the Journal of Clinical Medicine.
An autoimmune disease, MG occurs when the immune system produces self-reactive antibodies that bind to acetylcholine receptors or other proteins that are important for the communication between nerve and muscle cells. This leads to a range of symptoms, including muscle weakness and fatigue.
Azathioprine commonly used to treat myasthenia gravis
The standard treatment for myasthenia gravis is often with acetylcholinesterase inhibitors and corticosteroids at the lowest possible dose to minimize side effects, but azathioprine, an immunosuppressant, is also commonly used.
“Azathioprine … is used alone or in combination with corticosteroids to achieve remission or a minimally symptomatic state,” Modrego wrote. “In general, this treatment is well tolerated, but adverse events may occur sooner or later throughout the disease duration.”
In this study, Modrego set out to understand whether azathioprine can help patients live longer than standard treatment with pyridostigmine — an acetylcholinesterase inhibitor sold as Mestinon and generics — and prednisone, a corticosteroid.
The study included 90 adults diagnosed with MG (48 women, 42 men) who were followed for a mean of about 8.6 years. Their median age was 72. Seventy patients had generalized MG, which is marked by widespread muscle weakness and fatigue. Twenty had ocular MG, where symptoms are limited to the muscles that control the eye and eyelid movements.
Azathioprine was started in 38 patients, but seven stopped due to side effects and returned to standard treatment. Others tried other immunosuppressants, such as cyclosporine (sold as Neoral and others) and tacrolimus (marketed as Prograf and others), but some also stopped these therapies. In the end, 31 patients continued on azathioprine and were followed, along with 59 patients who did not receive azathioprine.
The unadjusted results showed patients who received azathioprine lived longer. However, when other factors were taken into account, age at the start of the study and disease type were the only factors significantly affecting survival. For every year increase in age, the risk of dying was increased by 12%.
Azathioprine reduced number of hospital visits, use of other medications
However, azathioprine reduced the number of hospital visits and the use of rescue medication in 16 patients. Fourteen participants stopped corticosteroids; the others needed lower doses. Patients on azathioprine had a lower mean number of exacerbations, when symptoms worsen or reappear, than those who didn’t receive azathioprine (6 vs. 9).
Three participants who were treated with azathioprine for more than 10 years developed cancer (two had forms of lung cancer and the third had Kaposi’s sarcoma). In the case of Kaposi’s sarcoma, which forms in the lining of blood vessels and lymph vessels, the cancer was effectively treated with appropriate cancer drugs and by stopping azathioprine. Two participants not treated with azathioprine also developed cancer (stomach and lung).
In total, four patients developed blood-related problems such as low red blood cells (anemia), a general reduction in all main types of blood cells (pancytopenia), and both anemia and low platelet counts (thrombocytopenia).
Causes of death in the group on azathioprine included pneumonia with sepsis (an extreme reaction to an infection), urinary infection with sepsis, respiratory insufficiency, and cardiac failure.
“The use of [azathioprine] in MG is beneficial,” Modrego concluded. “However, it does not seem to decrease mortality … compared to the standard treatment.” Because serious side effects can occur with azathioprine, regular monitoring is important, he noted.
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